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CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk

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ClinicalTrials.gov Identifier: NCT01050400
Recruitment Status : Completed
First Posted : January 15, 2010
Last Update Posted : August 28, 2017
Information provided by (Responsible Party):
Lawson Health Research Institute

January 11, 2010
January 15, 2010
August 28, 2017
February 24, 2009
December 31, 2012   (Final data collection date for primary outcome measure)
Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population [ Time Frame: 5-8 days post c-section surgery ]
Same as current
Complete list of historical versions of study NCT01050400 on ClinicalTrials.gov Archive Site
  • Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios. [ Time Frame: Minimum 1 week prior to c-section ]
  • Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment. [ Time Frame: Minimum 1 week prior to c-section ]
  • Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment. [ Time Frame: Minimum 1 week prior to c-section ]
Same as current
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CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.
Currently, the opioid analgesic codeine is commonly administered to breastfeeding mothers after Caesarean section for pain relief. Codeine was originally considered safe to use while breastfeeding however, increased risk of adverse drug reactions has been demonstrated in mothers taking codeine, as well as their breastfed infants, when the mother possesses a genetic variation resulting in cytochrome P450 2D6 (CYP2D6) ultra-rapid metabolizer (UM) phenotype. On average, most people convert about 10-15% of their codeine dose to morphine resulting in pain relief however, UM individuals can convert up to 50% of their codeine doses into active morphine. As many as 4% of North Americans may be UMs and these mothers and their breastfed infants are at high risk of serious adverse events despite "safe" codeine dosing due to morphine overproduction and accumulation in the mother and her breast milk. Observed side effects include severe sedation, decreased rate and depth of breathing and even infant death. In response to this problem, our hospital-based clinical trial strives to identify at-risk UM mother-infant pairs by performing a genetic test on non-invasive, voluntary saliva samples from mothers giving birth by Caesarean section and who will need codeine for pain relief while breastfeeding. We believe that this test will allow us to reliably identify at-risk UM mother-infant pairs and prevent adverse drug reactions in both by tailoring analgesic therapy to their genetic results: mothers identified as being UMs will be given other suitable analgesics, such as ibuprofen, in place of codeine-containing preparations. We propose that this prospective study will generate high-level data supporting the cost-effective genetic screening of mothers who will be taking codeine while breastfeeding before they begin taking their medications. Such testing is currently possible on a nation-wide scale through collaboration with the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).
Observational Model: Other
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Saliva and breast milk samples.
Probability Sample
Women undergoing elective caesarian section surgery and planning to breastfeed while concurrently taking codeine for post-partum pain relief within St. Joseph's Hospital in London and St. Michael's Hospital in Toronto.
Cytochrome P450 2D6 Ultra-rapid Metabolism
Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.
Genetic screening for cytochrome P450 2D6 (CYP2D6) polymorphism will be conducted on genetic information obtained from non-invasive salivary samples.
  • Observant
    Individuals within this group will receive pharmacotherapy according to the established institutional guidelines.
    Intervention: Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.
  • Prospective CYP2D6 genetic screening
    Individuals within the prospective group will receive their CYP2D6 genotype results prior to pharmacotherapy and their analgesic regimen will be tailored to their genetic results.
    Intervention: Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
December 31, 2012
December 31, 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Women who:

  • Have a pre-scheduled Caesarean section
  • Provide DNA for CYP2D6 genetic analysis
  • Breastfeed their infants
  • Take codeine-containing medication during breastfeeding (retrospective screening group and non-CYP2D6 ultrarapid metabolizers in prospective screening group)

Exclusion Criteria:

  • Mothers who do not provide consent prior to Caesarian section surgery
  • Mothers who take other sedative medications besides codeine during breastfeeding (these include benzodiazepines, skeletal muscle relaxants, psychotropic agents).
Sexes Eligible for Study: Female
Child, Adult, Senior
Contact information is only displayed when the study is recruiting subjects
Not Provided
Not Provided
Lawson Health Research Institute
Lawson Health Research Institute
Not Provided
Principal Investigator: Gideon Koren, MD University of Western Ontario, Canada
Lawson Health Research Institute
August 2017